title: Contrasting roles of E2F2 and E2F3 in cardiac neovascularization.
abstract: Insufficient neovascularization, characterized by poor endothelial cell (EC) growth, contributes to the pathogenesis of ischemic heart disease and limits cardiac tissue preservation and regeneration. The E2F family of transcription factors are critical regulators of the genes responsible for cell-cycle progression and growth; however, the specific roles of individual E2Fs in ECs are not well understood. Here we investigated the roles of E2F2 and E2F3 in EC growth, angiogenesis, and their functional impact on myocardial infarction (MI). An endothelial-specific E2F3-deficient mouse strain VE-Cre; E2F3(fl/fl) was generated, and MI was surgically induced in VE-Cre; E2F3(fl/fl) and E2F2-null (E2F2 KO) mice and their wild-type (WT) littermates, VE-Cre; E2F3(+/+) and E2F2 WT, respectively. The cardiac function, infarct size, and vascular density were significantly better in E2F2 KO mice and significantly worse in VE-Cre; E2F3(fl/fl) mice than in their WT littermates. The loss of E2F2 expression was associated with an increase in the proliferation of ECs both in vivo and in vitro, while the loss of E2F3 expression led to declines in EC proliferation. Thus, E2F3 promotes while E2F2 suppresses ischemic cardiac repair through corresponding changes in EC proliferation; and differential targeting of specific E2F members may provide a novel strategy for therapeutic angiogenesis of ischemic heart disease.
authors.affiliation: Feinberg Cardiovascular Research Institute, Department of Medicine-Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Junlan
authors.initials: J
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Shiyue
authors.initials: S
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.forename: Caizhi
authors.initials: C
authors.lastname: Ding
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.forename: Hongbin
authors.initials: H
authors.lastname: Yan
authors.forename: Dauren
authors.initials: D
authors.lastname: Biyashev
authors.forename: Raj
authors.initials: R
authors.lastname: Kishore
authors.forename: Gangjian
authors.initials: G
authors.lastname: Qin
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology*; D050703:E2F2 Transcription Factor / Q000502:physiology*; D050699:E2F3 Transcription Factor / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D016277:Ventricular Function, Left
chemical_list: D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; C484940:E2f2 protein, mouse; C490840:E2f3 protein, mouse